A perfusion system utilizing 25 ml of heparinized whole blood as a perfusate has been developed to study the metabolism of the isolated rat liver. Changes in the composition of the plasma of the perfusate were studied by circulation of the whole blood for 3 hours in the presence and absence of the liver. The discharge of glucose by the liver is marked by a pronounced initial hyperglycemia, which is countered slightly by red cell glycolysis. Despite continuous carbohydrate metabolism, a fall in sodium and a rise in potassium concentration occurs, ascribable chiefly to alteration of red blood cells. The hepatic glycogen content decreased slightly during perfusion. Urea production and bile flow were well preserved. Note: (With the Technical Assistance of Donna Cary and Veronica Mena) Submitted on June 26, 1959